As early as in 1971, Vane and his colleagues discovered that aspirin type nonsteroidal anti-inflammatory drug (NASID) have anti-inflammatory, analgesic and antifebrile functions by inhibiting Cyclooxygenase (CoX) and blocking prostaglandin synthesis from arachidonic acid. Vane et al also pointed out that the side effects caused by NSAID, such as irritation to stomach and intestines, and damages to kidney are also due to the elimination of the physiological prostaglandin which can protect stomach and kidney. Vane et al's views have been commonly accepted.
In the past twenty years, various researches have focused on the improvement of therapeutic effects of the NSAID and the reduction of the corresponding side effects through many methods, particularly on the improvement on the dosage forms of the medicines. For example, the medicines have been made into suppository, enteric-coated form and time-release form. There are also a substantial progress in the development of pharmaceuticals based on new chemicals and the development of the precursors.
In 1991, Herschman and Simmono using molecular cloning confirmed the second isoenzyme, named Cyclooxygenase-2 (CoX-2). Many subsequent literatures have demonstrated that CoX-2 is expressed in the inflammatory tissue and is controlled by glucocorticoid (GG). It is believed that CoX-2 can be the target of NSAID, which may provide a reasonable explanation for the side effects resulting from the inhibition of the CoX-1. Therefore, the discovery of CoX-2 has led the new trend of developing selective CoX-2 inhibitors.
It has been observed that many NSAID have a strong inhibiting effect on CoX-1 and a weak inhibiting effect on CoX-2. In other words, almost all the previously discovered NSAID can inhibit CoX-1. Furthermore, the stronger the inhibiting effect of a medicine has on CoX-1, the more side effects it has. While the stronger the inhibiting effect of a medicine exerts on CoX-2, the more effective the medicine is therapeutically. At present the ratio of CoX-1/Cox-2 is commonly used to express the effectiveness of inhibition of CoX-1 and CoX-2 by NSAID. The higher the ratio is, the stronger the inhibition of CoX-1 and in turn more side effects are. On the contrary, the lower the ratio is, the less the side effects.
At present, commercially available selective CoX-2 inhibitors are as follows:
(1) Meloxicam

This medicine is commercially available in many countries, and has been used to treat thousands of patients clinically. It is the representative of this type of medicine for treating osteoarthritis and rheumatic arthritis. (2) Celecoxib demonstrates the selective inhibition of CoX-2 by the animal arthritis and pain model. It also proves effectiveness in the similar treatment of human. The existing experimental results have demonstrated that in comparison with the previous NSAID, Celecoxib has an equavelent or better therapeutic effects and less side effects. (3) Vioxx has already been used clinically in the North America to treat osteoarthritis and release pain from tooth extraction. (4) Minesulide has already been used clinically in the United States and Europe.